Background: Growing up on traditional, single-family farms is associated with protection against asthma in school age, but the mechanisms against early manifestations of atopic disease are largely unknown. We sought determine the gut microbiome and metabolome composition in rural Old Order Mennonite (OOM) infants at low risk and Rochester, NY urban/suburban infants at high risk for atopic diseases. Methods: In a cohort of 65 OOM and 39 Rochester mother-infant pairs, 101 infant stool and 61 human milk samples were assessed by 16S rRNA gene sequencing for microbiome composition and qPCR to quantify Bifidobacterium spp. and B. longum ssp. infantis (B. infantis), a consumer of human milk oligosaccharides (HMOs). Fatty acids (FAs) were analyzed in 34 stool and human 24 milk samples. Diagnoses and symptoms of atopic diseases by 3 years of age were assessed by telephone.

BackgroundIn addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown.ObjectiveThis study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy.MethodsHM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA1 and IgA2 antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle.ResultsHM contains IgA1 and IgA2 antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and Streptococcus equii as well TGF-β2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto-N-neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with Prevotellaceae, Veillonellaceae, and Micrococcaceae cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA2 to dust mite, as well as of TSLP.ConclusionTraditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant’s gut microbiome and immune system.

Understanding how viral infections impact and are modulated by the microbiome is an important problem in basic research but is also of high clinical relevance under the current pandemic. To facilitate the study of interactions between microbial communities and pathogenic viruses under safe conditions, the infectious agent is generally inactivated prior to processing samples.

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